TY - JOUR
T1 - Cebulantin, a Cryptic Lanthipeptide Antibiotic Uncovered Using Bioactivity-Coupled HiTES
AU - Moon, Kyuho
AU - Xu, Fei
AU - Seyedsayamdost, Mohammad R.
N1 - Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/4/23
Y1 - 2019/4/23
N2 - The majority of natural product biosynthetic gene clusters in bacteria are silent under standard laboratory growth conditions, making it challenging to uncover any antibiotics that they may encode. Herein, bioactivity assays are combined with high-throughput elicitor screening (HiTES) to access cryptic, bioactive metabolites. Application of this strategy in Saccharopolyspora cebuensis, with inhibition of Escherichia coli growth as a read-out, led to the identification of a novel lanthipeptide, cebulantin. Extensive NMR spectroscopic analysis allowed the elucidation of the structure of cebulantin. Subsequent bioactivity assays revealed it to be an antibiotic selective for Gram-negative bacteria, especially against Vibrio species. This approach, referred to as bioactivity-HiTES, has the potential to uncover cryptic metabolites with desired biological activities that are hidden in microbial genomes.
AB - The majority of natural product biosynthetic gene clusters in bacteria are silent under standard laboratory growth conditions, making it challenging to uncover any antibiotics that they may encode. Herein, bioactivity assays are combined with high-throughput elicitor screening (HiTES) to access cryptic, bioactive metabolites. Application of this strategy in Saccharopolyspora cebuensis, with inhibition of Escherichia coli growth as a read-out, led to the identification of a novel lanthipeptide, cebulantin. Extensive NMR spectroscopic analysis allowed the elucidation of the structure of cebulantin. Subsequent bioactivity assays revealed it to be an antibiotic selective for Gram-negative bacteria, especially against Vibrio species. This approach, referred to as bioactivity-HiTES, has the potential to uncover cryptic metabolites with desired biological activities that are hidden in microbial genomes.
KW - HiTES
KW - cebulantin
KW - lanthipeptide
KW - natural products
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U2 - 10.1002/anie.201901342
DO - 10.1002/anie.201901342
M3 - Article
C2 - 30843641
AN - SCOPUS:85063597890
SN - 1433-7851
VL - 58
SP - 5973
EP - 5977
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 18
ER -